Functional analysis of yak alveolar type II epithelial cells at high and low altitudes based on single-cell sequencing

• Published in: Biochimica et biophysica acta. Molecular cell research 2025-02, Vol.1872 (2), p.119889, Article 119889
• Main Authors: Li, Jingyi, Huang, Nating, Zhang, Xun, Wang, Huizhen, Chen, Jiarui, Wei, Qing
• Format: Article
• Language: English
• Subjects: 10×scRNA-seq; AEC II; Altitude; Alveolar Epithelial Cells - cytology; Alveolar Epithelial Cells - metabolism; Animals; Cattle; Cell Transdifferentiation - genetics; Lung - cytology; Lung - metabolism; Single-Cell Analysis - methods; Transdifferentiation; Yak
• ISSN: 0167-4889; 1879-2596; 1879-2596
• DOI: 10.1016/j.bbamcr.2024.119889

The adaptation of lung cells to high-altitude environments represents a notable gap in our understanding of how animals cope with hypoxic conditions. Alveolar epithelial cells type II (AEC II) are crucial for lung development and repair. However, their, specific role in the adaptation of yaks to high-altitude environments remains unclear. In this study, we aimed to address this gap by investigating the differential responses of AEC II in yaks at high and low altitudes (4000 m and 2600 m, respectively). We used the 10 × scRNA-seq technology to construct a comprehensive cell atlas of yak lung tissue, and identified 15 distinct cell classes. AEC II in high-altitude yaks revealed increased immunomodulatory, adhesive, and metabolic activities, which are crucial for maintaining lung tissue stability and energy supply under hypoxic conditions. Furthermore, alveolar epithelial progenitor cells within AEC II can differentiate into both Alveolar epithelial cell type I (AEC I) and AEC II. SHIP1 and other factors are promoters of AEC I transdifferentiation, whereas SFTPC and others promote AEC II transdifferentiation. This study provides new insights into the evolutionary adaptation of lung cells in plateau animals by elucidating the molecular mechanisms underlying AEC II adaptation to high-altitude environments. [Display omitted] •Yak lung tissue cell atlas was constructed using 10×scRNA-seq technique, and the lung tissue was divided and merged into 15 major cell classes.•Enhanced immune, adhesion and metabolic processes of AEC II in lung tissue of yaks at high altitude compared to yaks at low altitude.•Based on the results of alveolar epithelial cell re-population, using chronoanalysis s technique we hypothesized that there may also be an alveolar epithelial progenitor cell within the alveolar epithelial cells, which can be re-differentiated into AEC I and AEC II, and that there is a potential differentiation relationship between AEC II and AEC I as well.